{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:06:23Z","timestamp":1789977983854,"version":"4.0.1"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["nyaspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann NY Acad Sci"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    DLX3 is a homeobox transcription factor essential for multiple organogenesis processes. Mutations in\n                    <jats:italic>DLX3<\/jats:italic>\n                    cause trichodentoosseous syndrome (TDO), characterized by curly hair, sclerotic bone, enamel, and dentin defects as well as taurodontism. Phenotypic variability in TDO has been well documented, but its pathogenesis remains poorly understood. Here, we characterized three TDO families with distinct clinical features and identified a known\n                    <jats:italic>DLX3<\/jats:italic>\n                    deletion (c.561_562del) and the first pathogenic splice\u2010site variant (c.516+1_516+2insA). The proband with the splice\u2010site mutation displayed a mesenchymal\u2010dominant phenotype with severe dentin hypoplasia, enlarged pulp chambers, and hypertaurodontism but nearly normal enamel, whereas the mother and sister showed epithelial\u2010dominant anomalies, including enamel hypoplasia and kinky hair. Minigene analysis demonstrated that c.516+1_516+2insA generated two aberrant transcripts encoding p.Val173Aspfs*28 and p.Arg120_Val173del. These mutant proteins localized mainly in the cytoplasm and showed markedly reduced transactivation activity. In cultured human dental pulp cells,\n                    <jats:italic>DLX3<\/jats:italic>\n                    overexpression upregulated the odontoblastic markers\n                    <jats:italic>DSPP<\/jats:italic>\n                    ,\n                    <jats:italic>MMP20<\/jats:italic>\n                    , and\n                    <jats:italic>WNT10A<\/jats:italic>\n                    . Chromatin immunoprecipitation and reporter assays further revealed that DLX3 directly activates\n                    <jats:italic>WNT10A<\/jats:italic>\n                    via a conserved enhancer (chr2:218,878,973_218,879,302) and three upstream binding sites. These findings expand the TDO mutational spectrum and suggest that differential mutant\n                    <jats:italic>DLX3<\/jats:italic>\n                    expression may contribute to phenotypic variability, whereas disrupted regulation of\n                    <jats:italic>WNT10A<\/jats:italic>\n                    underlies dentin defects and taurodontism.\n                  <\/jats:p>","DOI":"10.1111\/nyas.70228","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:03:14Z","timestamp":1772989394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential Effects of\n                    <i>DLX3<\/i>\n                    Mutations Drive Phenotypic Variability in Tricho\u2010Dento\u2010Osseous Syndrome via Direct Activation of\n                    <i>WNT10A<\/i>"],"prefix":"10.1111","volume":"1557","author":[{"given":"Yin\u2010Lin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Dentistry National Taiwan University School of Dentistry  Taipei City Taiwan"},{"name":"Department of Pediatric Dentistry National Taiwan University Children's Hospital  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua\u2010Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Dentistry National Taiwan University School of Dentistry  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung\u2010Tsu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dentistry National Taiwan University School of Dentistry  Taipei City Taiwan"},{"name":"Department of Dentistry National Taiwan University Hospital  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiao\u2010Hua","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dentistry National Taiwan University School of Dentistry  Taipei City Taiwan"},{"name":"Department of Pediatric Dentistry National Taiwan University Children's Hospital  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Feng","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry National Taiwan University Children's Hospital  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin\u2010Ya","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry National Taiwan University Children's Hospital  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih\u2010Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dentistry National Taiwan University School of Dentistry  Taipei City Taiwan"},{"name":"Department of Pediatric Dentistry National Taiwan University Children's Hospital  Taipei City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"569","article-title":"The Tricho\u2010Dento\u2010Osseous (TDO) Syndrome","volume":"24","author":"Lichtenstein J.","year":"1972","journal-title":"American Journal of Human 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